The use of biochemical bone turnover markers (BTMs) in clinical trials has been helpful in understanding the mechanism of action of therapeutic agents. However, their role in the care of individual patients is not well established. Biologic and laboratory variability in BTM values have confounded their widespread use in clinical practice (table 1). BTMs have little value for the diagnosis of osteoporosis, because dual-energy x-ray absorptiometry (DXA) is far superior for this purpose. However, markers of bone turnover give some indication about the future risk for bone loss and fractures. More importantly, they are useful in monitoring the efficacy of antiresorptive therapy in patients with osteoporosis.
This topic will review these issues. The rationale for the use of biochemical markers and the meaning of the different markers are discussed separately. (See "Bone physiology and biochemical markers of bone turnover".) The use of BTMs in other bone disorders is also reviewed separately. (See "Investigational biologic markers in the diagnosis and assessment of rheumatoid arthritis" and "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma".)
The mean values for biochemical markers of bone turnover are higher in patients with osteoporosis than in matched normal subjects. As an example, the mean urinary excretion of deoxypyridinoline crosslinks (DPD, a marker of bone resorption) is 20 to 100 percent higher in patients with osteoporosis than in normal subjects [1-4]. The results of measurements of other markers are similar [1-3,5].
In addition, bone mineral density in patients with osteoporosis is inversely related to the levels of markers of bone turnover. One study, for example, found a highly significant correlation between serum osteocalcin concentrations (a marker of bone formation) and bone mineral density of the spine . Another report divided subjects into quintiles according to the urinary excretion of cross-linked N-telopeptides (NTX) of type I collagen, a marker of bone resorption . There was an inverse relationship between the quintile of urinary N-telopeptide excretion and mean bone mineral density (figure 1). These findings are consistent with the concept that osteoporosis is characterized by an increase in both bone formation and resorption. (See "Pathogenesis of osteoporosis".)
Despite these general trends, biochemical markers are not useful in making the diagnosis of osteoporosis because the values in normal subjects and patients with osteoporosis overlap substantially (figure 2). For this reason, we do not recommend measurements of markers of bone turnover to make a diagnosis of osteoporosis.